Most, if not all, organisms contain within their genomes multiple copies of discrete DNA sequences that are capable of transposition to and excision from many different chromosomal sites. These DNA sequences are collectively termed transposable genetic elements, or transposons. Transposable elements are a major source of spontaneous mutations in these organisms. They may be responsible for a significant portion of genetic variability and genetic load that occurs in nature. Transposition and excision of transposable elements is tightly controlled in many species. The frequencies of transposition and excision can be regulated in a strain- and tissue-specific manner. Genetic activity of the transposable element Tc1, contained in the nematode Caenorhabditis elegans, is subject to both strain-specific and tissue-specific regulation. We will investigate the genetic and molecular basis for strain-specific and, tissue-specific activity of Tc1. Our goals are: 1. To identify and clone the transposable element that expresses the transposase function on which Tc1 depends for its activity. 2. To sequence this element and define the transposase gene(s) within it. 3. To determine the strains and tissues in which this transposase gene is expressed. We will test the working model that strain- specific and tissue-specific expression of the autonomous element is responsible for strain-specific and tissue-specific activity of Tc1. Our methods involve a combination of traditional genetic and molecular genetic techniques. This research contributes to the national health by describing in molecular detail an important mechanism for natural mutation. Understanding the genetic biology of transposons will contribute to our understanding of genetic diseases in general.